The identification of patients with possible sepsis is vitally important because timely recognition and appropriate, effective treatment substantially improves survival. Unlike some other life-threatening conditions (such as myocardial infarction), for which highly accurate diagnostic tests are available, no rapid diagnostic tests are currently available to accurately identify patients with sepsis (or those at high risk of developing sepsis) to help clinicians determine the best course of action. Development of such tests for sepsis will involve consideration of a number of key issues, such as whether sepsis is just one or, rather, multiple entities; whether degrees of having sepsis exist; which test is the gold standard (an accepted benchmark against which similar tests can be compared and diagnostic accuracy assessed); what levels of accuracy are sufficient for use in clinical practice; and which tests based on what markers are the most cost-effective. In the meantime, however, clinicians must rely on clinical judgment, potentially augmented by clinical criteria validated to identify sepsis among patients with infection.